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. 1991 Nov;88(5):1481–1489. doi: 10.1172/JCI115458

Failure of atrial natriuretic factor to increase with saline load in patients with dilated cardiomyopathy and mild heart failure.

M Volpe 1, C Tritto 1, N De Luca 1, A F Mele 1, G Lembo 1, S Rubattu 1, M Romano 1, P De Campora 1, I Enea 1, B Ricciardelli 1, et al.
PMCID: PMC295653  PMID: 1834698

Abstract

To investigate whether the response of atrial natriuretic factor (ANF) to volume expansion is impaired in the early stages of dilated cardiomyopathy, the effects of saline load (SL; 0.25 ml/kg.min for 120 min) were assessed in 12 patients with dilated cardiomyopathy and asymptomatic to mildly symptomatic heart failure (HF) and in nine normal subjects (N). SL increased plasma ANF levels in N (from 14.3 +/- 2 to 19.5 +/- 3 and 26 +/- 4 pg/ml, at 60 and 120 min, respectively, P less than 0.001), but not in HF (from 42.9 +/- 9 to 45.9 +/- 9 and 43.9 +/- 8 pg/ml). Left ventricular end-diastolic volume (LVEDV) and stroke volume were increased (P less than 0.001) by SL in N but not in HF. Urinary sodium excretion (UNaV) increased in N more than in HF during SL, whereas forearm vascular resistance (FVR) did not change in N and increased in HF (P less than 0.001). In five HF patients SL was performed during ANF infusion (50 ng/kg, 5 ng/kg.min) that increased ANF levels from 37.1 +/- 10 to 146 +/- 22 pg/ml. In this group, SL raised both LVEDV (P less than 0.01) and ANF (P less than 0.05), whereas FVR did not rise. In addition, the UNaV increase and renin and aldosterone suppressions by SL were more marked than those observed in HF under control conditions. Thus, in patients with dilated cardiomyopathy and mild cardiac dysfunction, plasma ANF levels are not increased by volume expansion as observed in N. The lack of ANF response is related to the impaired cardiac adaptations. The absence of an adequate increase of ANF levels may contribute to the abnormal responses of HF patients to saline load.

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  1. ANTON A. H., SAYRE D. F. A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines. J Pharmacol Exp Ther. 1962 Dec;138:360–375. [PubMed] [Google Scholar]
  2. Bates E. R., Shenker Y., Grekin R. J. The relationship between plasma levels of immunoreactive atrial natriuretic hormone and hemodynamic function in man. Circulation. 1986 Jun;73(6):1155–1161. doi: 10.1161/01.cir.73.6.1155. [DOI] [PubMed] [Google Scholar]
  3. Bolli P., Müller F. B., Linder L., Raine A. E., Resink T. J., Erne P., Kiowski W., Ritz R., Bühler F. R. The vasodilator potency of atrial natriuretic peptide in man. Circulation. 1987 Jan;75(1):221–228. doi: 10.1161/01.cir.75.1.221. [DOI] [PubMed] [Google Scholar]
  4. Burnett J. C., Jr, Kao P. C., Hu D. C., Heser D. W., Heublein D., Granger J. P., Opgenorth T. J., Reeder G. S. Atrial natriuretic peptide elevation in congestive heart failure in the human. Science. 1986 Mar 7;231(4742):1145–1147. doi: 10.1126/science.2935937. [DOI] [PubMed] [Google Scholar]
  5. Cavero P. G., Margulies K. B., Winaver J., Seymour A. A., Delaney N. G., Burnett J. C., Jr Cardiorenal actions of neutral endopeptidase inhibition in experimental congestive heart failure. Circulation. 1990 Jul;82(1):196–201. doi: 10.1161/01.cir.82.1.196. [DOI] [PubMed] [Google Scholar]
  6. Chien Y. W., Barbee R. W., MacPhee A. A., Frohlich E. D., Trippodo N. C. Increased ANF secretion after volume expansion is preserved in rats with heart failure. Am J Physiol. 1988 Feb;254(2 Pt 2):R185–R191. doi: 10.1152/ajpregu.1988.254.2.R185. [DOI] [PubMed] [Google Scholar]
  7. Cody R. J., Atlas S. A., Laragh J. H., Kubo S. H., Covit A. B., Ryman K. S., Shaknovich A., Pondolfino K., Clark M., Camargo M. J. Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion. J Clin Invest. 1986 Nov;78(5):1362–1374. doi: 10.1172/JCI112723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cody R. J., Covit A. B., Schaer G. L., Laragh J. H., Sealey J. E., Feldschuh J. Sodium and water balance in chronic congestive heart failure. J Clin Invest. 1986 May;77(5):1441–1452. doi: 10.1172/JCI112456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cuocolo A., Esposito S., Acampora C., Squame G. Diagnosi di cardiopatia ischemica in pazienti ipertesi. Confronto tra tecniche radioisotopiche. Radiol Med. 1988 Mar;75(3):160–165. [PubMed] [Google Scholar]
  10. Drexler H., Hirth C., Stasch H. P., Lu W., Neuser D., Just H. Vasodilatory action of endogenous atrial natriuretic factor in a rat model of chronic heart failure as determined by monoclonal ANF antibody. Circ Res. 1990 May;66(5):1371–1380. doi: 10.1161/01.res.66.5.1371. [DOI] [PubMed] [Google Scholar]
  11. Edwards B. S., Ackermann D. M., Lee M. E., Reeder G. S., Wold L. E., Burnett J. C., Jr Identification of atrial natriuretic factor within ventricular tissue in hamsters and humans with congestive heart failure. J Clin Invest. 1988 Jan;81(1):82–86. doi: 10.1172/JCI113314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ferguson D. W., Abboud F. M., Mark A. L. Selective impairment of baroreflex-mediated vasoconstrictor responses in patients with ventricular dysfunction. Circulation. 1984 Mar;69(3):451–460. doi: 10.1161/01.cir.69.3.451. [DOI] [PubMed] [Google Scholar]
  13. Floras J. S. Sympathoinhibitory effects of atrial natriuretic factor in normal humans. Circulation. 1990 Jun;81(6):1860–1873. doi: 10.1161/01.cir.81.6.1860. [DOI] [PubMed] [Google Scholar]
  14. Folland E. D., Parisi A. F., Moynihan P. F., Jones D. R., Feldman C. L., Tow D. E. Assessment of left ventricular ejection fraction and volumes by real-time, two-dimensional echocardiography. A comparison of cineangiographic and radionuclide techniques. Circulation. 1979 Oct;60(4):760–766. doi: 10.1161/01.cir.60.4.760. [DOI] [PubMed] [Google Scholar]
  15. Fujita T., Ito Y., Noda H., Sato Y., Ando K., Kangawa K., Matsuo H. Vasodilatory actions of alpha-human atrial natriuretic peptide and high Ca2+ effects in normal man. J Clin Invest. 1987 Sep;80(3):832–840. doi: 10.1172/JCI113141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gibbs D. M. Noncalcium-dependent modulation of in vitro atrial natriuretic factor release by extracellular osmolality. Endocrinology. 1987 Jan;120(1):194–197. doi: 10.1210/endo-120-1-194. [DOI] [PubMed] [Google Scholar]
  17. Gottlieb S. S., Kukin M. L., Ahern D., Packer M. Prognostic importance of atrial natriuretic peptide in patients with chronic heart failure. J Am Coll Cardiol. 1989 Jun;13(7):1534–1539. doi: 10.1016/0735-1097(89)90344-6. [DOI] [PubMed] [Google Scholar]
  18. Greenwald J. E., Sakata M., Michener M. L., Sides S. D., Needleman P. Is atriopeptin a physiological or pathophysiological substance? Studies in the autoimmune rat. J Clin Invest. 1988 Apr;81(4):1036–1041. doi: 10.1172/JCI113414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hintze T. H., Wang J., Patel M., Schustek M., Ochoa M., Dean R., Chiruzzo F., Zeballos G. Dynamics of atrial peptide secretion in the coronary circulation of the conscious dog. Circ Res. 1990 Sep;67(3):609–614. doi: 10.1161/01.res.67.3.609. [DOI] [PubMed] [Google Scholar]
  20. Holmer S. R., Riegger A. J., Notheis W. F., Kromer E. P., Kochsiek K. Hemodynamic changes and renal plasma flow in early heart failure: implications for renin, aldosterone, norepinephrine, atrial natriuretic peptide and prostacyclin. Basic Res Cardiol. 1987 Mar-Apr;82(2):101–108. doi: 10.1007/BF01907058. [DOI] [PubMed] [Google Scholar]
  21. Kamoi K., Sato F., Arai O., Ishibashi M., Yamaji T. Effects of plasma volume and osmolality on secretion of atrial natriuretic peptide and vasopressin in man. Acta Endocrinol (Copenh) 1988 May;118(1):51–58. doi: 10.1530/acta.0.1180051. [DOI] [PubMed] [Google Scholar]
  22. Kirkendall W. M., Burton A. C., Epstein F. H., Freis E. D. Recommendations for human blood pressure determination by sphygmomanometers. Circulation. 1967 Dec;36(6):980–988. doi: 10.1161/01.cir.36.6.980. [DOI] [PubMed] [Google Scholar]
  23. Laragh J. H. Atrial natriuretic hormone, the renin-aldosterone axis, and blood pressure-electrolyte homeostasis. N Engl J Med. 1985 Nov 21;313(21):1330–1340. doi: 10.1056/NEJM198511213132106. [DOI] [PubMed] [Google Scholar]
  24. Lee M. E., Miller W. L., Edwards B. S., Burnett J. C., Jr Role of endogenous atrial natriuretic factor in acute congestive heart failure. J Clin Invest. 1989 Dec;84(6):1962–1966. doi: 10.1172/JCI114385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lee R. W., Gay R. G., Moffett C., Johnson D. G., Goldman S. Atrial natriuretic peptide levels during development of chronic heart failure after myocardial infarction in rats. Life Sci. 1987 May 18;40(20):2025–2030. doi: 10.1016/0024-3205(87)90294-3. [DOI] [PubMed] [Google Scholar]
  26. Menard J., Catt K. J. Measurement of renin activity, concentration and substrate in rat plasma by radioimmunoassay of angiotensin I. Endocrinology. 1972 Feb;90(2):422–430. doi: 10.1210/endo-90-2-422. [DOI] [PubMed] [Google Scholar]
  27. Mendez R. E., Pfeffer J. M., Ortola F. V., Bloch K. D., Anderson S., Seidman J. G., Brenner B. M. Atrial natriuretic peptide transcription, storage, and release in rats with myocardial infarction. Am J Physiol. 1987 Dec;253(6 Pt 2):H1449–H1455. doi: 10.1152/ajpheart.1987.253.6.H1449. [DOI] [PubMed] [Google Scholar]
  28. Moe G. W., Grima E. A., Angus C., Wong N. L., Hu D. C., Howard R. J., Armstrong P. W. Response of atrial natriuretic factor to acute and chronic increases of atrial pressures in experimental heart failure in dogs. Role of changes in heart rate, atrial dimension, and cardiac tissue concentration. Circulation. 1991 May;83(5):1780–1787. doi: 10.1161/01.cir.83.5.1780. [DOI] [PubMed] [Google Scholar]
  29. Nakaoka H., Imataka K., Amano M., Fujii J., Ishibashi M., Yamaji T. Plasma levels of atrial natriuretic factor in patients with congestive heart failure. N Engl J Med. 1985 Oct 3;313(14):892–893. doi: 10.1056/NEJM198510033131416. [DOI] [PubMed] [Google Scholar]
  30. Raine A. E., Erne P., Bürgisser E., Müller F. B., Bolli P., Burkart F., Bühler F. R. Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure. N Engl J Med. 1986 Aug 28;315(9):533–537. doi: 10.1056/NEJM198608283150901. [DOI] [PubMed] [Google Scholar]
  31. Redfield M. M., Edwards B. S., McGoon M. D., Heublein D. M., Aarhus L. L., Burnett J. C., Jr Failure of atrial natriuretic factor to increase with volume expansion in acute and chronic congestive heart failure in the dog. Circulation. 1989 Sep;80(3):651–657. doi: 10.1161/01.cir.80.3.651. [DOI] [PubMed] [Google Scholar]
  32. Riegger G. A., Kochsiek K. Vasopressin, renin and norepinephrine levels before and after captopril administration in patients with congestive heart failure due to idiopathic dilated cardiomyopathy. Am J Cardiol. 1986 Aug 1;58(3):300–303. doi: 10.1016/0002-9149(86)90066-4. [DOI] [PubMed] [Google Scholar]
  33. Rodeheffer R. J., Tanaka I., Imada T., Hollister A. S., Robertson D., Inagami T. Atrial pressure and secretion of atrial natriuretic factor into the human central circulation. J Am Coll Cardiol. 1986 Jul;8(1):18–26. doi: 10.1016/s0735-1097(86)80086-9. [DOI] [PubMed] [Google Scholar]
  34. Ruskoaho H., Vakkuri O., Arjamaa O., Vuolteenaho O., Leppäluoto J. Pressor hormones regulate atrial-stretch-induced release of atrial natriuretic peptide in the pithed rat. Circ Res. 1989 Mar;64(3):482–492. doi: 10.1161/01.res.64.3.482. [DOI] [PubMed] [Google Scholar]
  35. Saito Y., Nakao K., Arai H., Nishimura K., Okumura K., Obata K., Takemura G., Fujiwara H., Sugawara A., Yamada T. Augmented expression of atrial natriuretic polypeptide gene in ventricle of human failing heart. J Clin Invest. 1989 Jan;83(1):298–305. doi: 10.1172/JCI113872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Thomas J. A., Marks B. H. Plasma norepinephrine in congestive heart failure. Am J Cardiol. 1978 Feb;41(2):233–243. doi: 10.1016/0002-9149(78)90162-5. [DOI] [PubMed] [Google Scholar]
  37. Thorén P., Mark A. L., Morgan D. A., O'Neill T. P., Needleman P., Brody M. J. Activation of vagal depressor reflexes by atriopeptins inhibits renal sympathetic nerve activity. Am J Physiol. 1986 Dec;251(6 Pt 2):H1252–H1259. doi: 10.1152/ajpheart.1986.251.6.H1252. [DOI] [PubMed] [Google Scholar]
  38. Tikkanen I., Fyhrquist F., Metsärinne K., Leidenius R. Plasma atrial natriuretic peptide in cardiac disease and during infusion in healthy volunteers. Lancet. 1985 Jul 13;2(8446):66–69. doi: 10.1016/s0140-6736(85)90178-3. [DOI] [PubMed] [Google Scholar]
  39. Tsunoda K., Hodsman G. P., Sumithran E., Johnston C. I. Atrial natriuretic peptide in chronic heart failure in the rat: a correlation with ventricular dysfunction. Circ Res. 1986 Sep;59(3):256–261. doi: 10.1161/01.res.59.3.256. [DOI] [PubMed] [Google Scholar]
  40. Uretsky B. F., Verbalis J. G., Murali S., Betschart A. R., Kolesar J. A., Reddy P. S. Control of atrial natriuretic peptide secretion in patients with severe congestive heart failure. J Clin Endocrinol Metab. 1990 Jul;71(1):146–151. doi: 10.1210/jcem-71-1-146. [DOI] [PubMed] [Google Scholar]
  41. Volpe M., Cuocolo A., Vecchione F., Mele A. F., Condorelli M., Trimarco B. Vagal mediation of the effects of atrial natriuretic factor on blood pressure and arterial baroreflexes in the rabbit. Circ Res. 1987 May;60(5):747–755. doi: 10.1161/01.res.60.5.747. [DOI] [PubMed] [Google Scholar]
  42. Volpe M., De Luca N., Bigazzi M. C., Vecchione F., Lembo G., Condorelli M., Trimarco B. Atrial natriuretic factor potentiates forearm reflex vasoconstriction induced by cardiopulmonary receptor deactivation in man. Circulation. 1988 Apr;77(4):849–855. doi: 10.1161/01.cir.77.4.849. [DOI] [PubMed] [Google Scholar]
  43. Volpe M., Lembo G., Condorelli G., De Luca N., Lamenza F., Indolfi C., Trimarco B. Converting enzyme inhibition prevents the effects of atrial natriuretic factor on baroreflex responses in humans. Circulation. 1990 Oct;82(4):1214–1221. doi: 10.1161/01.cir.82.4.1214. [DOI] [PubMed] [Google Scholar]
  44. Yasue H., Obata K., Okumura K., Kurose M., Ogawa H., Matsuyama K., Jougasaki M., Saito Y., Nakao K., Imura H. Increased secretion of atrial natriuretic polypeptide from the left ventricle in patients with dilated cardiomyopathy. J Clin Invest. 1989 Jan;83(1):46–51. doi: 10.1172/JCI113883. [DOI] [PMC free article] [PubMed] [Google Scholar]

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